Major requirements for materials used as a substrate or a scaffold for the regeneration of human tissues are promotion of excellent cell adhesion and proliferation, and maintenance of integrity for the differentiated cell functions. Furthermore, the materials should be well deliquesced with contiguous tissues after transplantation without inflammatory reaction, and they should self-deteriorate after a predetermined period so that they do not remain in vivo as gratuitous materials.
Known, conventional materials having acceptable absorption rates in the living body include natural and synthetic polymers such as collagen, gelatin, hyaluronic acid, pectin, and cellulose derivatives. The porous scaffolds were introduced for the purpose of cell or tissue culture and transplantation, cosmetics, medical materials such as wound coverings and dental matrix. Among these various uses, Japanese patent laid-open No. 7-313585 discloses a method for manufacturing scaffolds using hyaluronic acid, wherein the hyaluronic acid scaffolds, cross-linked by an epoxy compound and thrombin-added hyaluronic acid, are used as wound coverings. In addition, WO 94/02517 suggests a method for manufacturing insoluble hyaluronic acid derivate scaffolds through cross-linking of carbodiimide.
However, those scaffolds manufactured by using only hyaluronic acid are easy to break, and they are very soluble in water or in body fluids unless they are cross-linked. Therefore, cross-linking materials such as divinylsulfone, formaldehyde, carbodiimide and epoxy compounds have to be used for providing the mechanical properties necessary for manufacturing scaffolds. Since unreacted divinylsulfone and aldehyde cause cytotoxicity in the living body, use of the same are restricted.
Natural polymers have the advantage of source as natural substances so that they are inherently compatible to a living body. However, there are disadvantages such as relatively high tissue rejection reactivity and infection rate, and it is difficult to control their decomposition properties. Also, there have been reports that their mechanical properties are weak in an aqueous environment.
Thus, active studies on biodegradable synthetic polymers have been carried out. The basic structure of a biodegradable synthetic polymer consists of an absorbable structure and a degradable structure; structures capable of hydrolysis are used for the latter. Aliphatic polyesters having excellent physical characteristics and hydrolysis property are proposed for materials as biodegradable synthetic polymers. Currently used biodegradable synthetic polymers are polyamino acid, polyanhydride, polycaprolactone, polyglycolide, polylactide and their derivatives, i.e., lactide and glycolide copolymers.
Currently porous polymeric scaffolds using biodegradable polymers such as polyglycolide, polylactide, lactidelglycolide copolymer are commonly used. However, they have limited physical properties which puts great limitations as use for regeneration materials for human tissue or organ, which requires versatile physical properties. Especially, elasticity is an essential property for muscular tissues constituting skeletal muscles, smooth muscles, heart muscles and the like, and the elastic scaffold materials are expected to have distinguished effects in the regeneration of such elastic tissues.
Further, there have been reports that mechanical stimulation during culture of cell lines in a scaffold makes the cells stronger, which is very advantageous in tissue regeneration (B. S. Kim, J. Nikolovski, E. Smiley, J. Bonadio and D. J. Mooney, Bioengineering Conference, 42, 27˜28, 1999).
Biodegradable polymers such as polyglycolide and polycaprolactone have low immunity and negligible toxicity, and is suitable for medical uses. In particular, poly-glycolides have superior mechanical properties (D. L. Wise et al., “Drug Carries in Biology and Medicine”, 1st ed., G. Gregoriadis, Ed., Academic Press, New York, 237-270, 1979).
On selecting biodegradable polymeric materials for preparing a porous scaffold for tissue engineering, one must consider that the materials should cause the growth of the cells in tissue, maintain the function of differentiated cells, be well deliquesced with contiguous tissues after transplantation without inflammatory reaction, and should self-deteriorate after a predetermined time so that they do not remain in vivo as gratuitous materials.